Salmonella is a genus of over 2000 serovars and includes organisms that cause a wide range of human and animal diseases. For example, Salmonella enterica serovars Typhi and Paratyphi A and B cause enteric (“typhoid”) fever. Salmonella enterica serovars Typhimurium and Enteritidis are known as the non-typhoidal Salmonella (NTS) and cause salmonellosis—a gastroenteritis which is usually a self-limiting illness in healthy individuals.
As is the case with many gram-negative pathogens, Salmonella spp. use type III secretion systems (T3SSs) as virulence factors to deliver proteins into host cells and to subsequently cause/induce infection. The T3SS is a molecular “syringe and needle” apparatus, also known as a “type III secretion apparatus” (T3SA) which promotes uptake of the bacterium by the host cell, and then adaptation of the intracellular environment of the host cell to allow a productive infection. Salmonella has two functionally distinct T3SS's which are encoded by Salmonella “pathogenicity islands” 1 and 2 (SPI-1 and -2). The SPI-1 T3SS is central to the ability of Salmonella to invade nonphagocytic cells via the injection, from the bacteria and into the cell by way of the T3SA conduit, effector proteins which trigger extensive actin rearrangements on the surface of host cells. While this allows ingress of the pathogen into the host cell, a second T3SS island, SPI-2, is essential for bacterial replication/proliferation inside host cells. Upon intracellular activation of SPI-2, the bacteria proliferate within membrane-bound vacuoles of phagocytic eukaryotic cells (Salmonella-containing vacuoles, SCVs), with macrophages being the main cell type supporting bacterial growth in vivo. Bacterial effector proteins are translocated across the vacuolar membrane via the SPI-2 T3SS apparatus and into the host endomembrane system and cytoplasm, causing systemic disease.
The Salmonella NTS serotypes are a primary cause of foodborne illnesses worldwide. In the U.S. NTS are a leading cause of hospitalization and death due to foodborne illnesses, with Salmonella enterica serovar Typhimurium being the most frequent cause. 95% of the total cases of NTS are caused by contaminated food. Unfortunately, absolute protection from infection by enhanced agricultural surveillance is not feasible. Vaccines against these pathogens could provide a major weapon in controlling this disease. However, although some progress has been made in recent years, vaccines against Salmonella spp. have not proven to be broadly protective, and almost all are entirely directed only to the typhoid causing serovars. A Salmonella serotype-independent subunit vaccine that could target both typhoid and NTS serovars would be of tremendous public health value.